Risk prediction of fever in neutropenia in children with cancer: a step towards individually tailored supportive therapy?

BACKGROUND: Fever in severe chemotherapy-induced neutropenia (FN) is the most frequent manifestation of a potentially lethal complication of current intensive chemotherapy regimens. This study aimed at establishing models predicting the risk of FN, and of FN with bacteremia, in pediatric cancer patients. METHODS: In a single-centre cohort study, characteristics potentially associated with FN and episodes of FN were retrospectively extracted from charts. Poisson regression accounting for chemotherapy exposure time was used for analysis. Prediction models were constructed based on a derivation set of two thirds of observations, and validated based on the remaining third of observations. RESULTS: In 360 pediatric cancer patients diagnosed and treated for a cumulative chemotherapy exposure time of 424 years, 629 FN were recorded (1.48 FN per patient per year, 95% confidence interval (CI), 1.37-1.61), 145 of them with bacteremia (23% of FN; 0.34; 0.29-0.40). More intensive chemotherapy, shorter time since diagnosis, bone marrow involvement, central venous access device (CVAD), and prior FN were significantly and independently associated with a higher risk to develop both FN and FN with bacteremia. The prediction models explained more than 30% of the respective risks. CONCLUSIONS: The two models predicting FN and FN with bacteremia were based on five easily accessible clinical variables. Before clinical application, they need to be validated by prospective studies.

Mannose-binding lectin cord blood levels and respiratory symptoms during infancy: a prospective birth cohort study

Respiratory infections cause considerable morbidity during infancy. The impact of innate immunity mechanisms, such as mannose-binding lectin (MBL), on respiratory symptoms remains unclear. The aims of this study were to investigate whether cord blood MBL levels are associated with respiratory symptoms during infancy and to determine the relative contribution of MBL when compared with known risk factors. This is a prospective birth cohort study including 185 healthy term infants. MBL was measured in cord blood and categorized into tertiles. Frequency and severity of respiratory symptoms were assessed weekly until age one. Association with MBL levels was analysed using multivariable random effects Poisson regression. We observed a trend towards an increased incidence rate of severe respiratory symptoms in infants in the low MBL tertile when compared with infants in the middle MBL tertile [incidence rate ratio (IRR) = 1.59; 95% confidence interval (CI): 0.95-2.66; p = 0.076]. Surprisingly, infants in the high MBL tertile suffered significantly more from severe and total respiratory symptoms than infants in the middle MBL tertile (IRR = 1.97; 95% CI: 1.20-3.25; p = 0.008). This association was pronounced in infants of parents with asthma (IRR = 3.64; 95% CI: 1.47-9.02; p = 0.005). The relative risk associated with high MBL was similar to the risk associated with well-known risk factors such as maternal smoking or childcare. In conclusion the association between low MBL levels and increased susceptibility to common respiratory infections during infancy was weaker than that previously reported. Instead, high cord blood MBL levels may represent a so far unrecognized risk factor for respiratory morbidity in infants of asthmatic parents.

Sexual transmission of HIV according to viral load and antiretroviral therapy: systematic review and meta-analysis

OBJECTIVES: To synthesize the evidence on the risk of HIV transmission through unprotected sexual intercourse according to viral load and treatment with combination antiretroviral therapy (ART). DESIGN: Systematic review and meta-analysis. METHODS: We searched Medline, Embase and conference abstracts from 1996-2009. We included longitudinal studies of serodiscordant couples reporting on HIV transmission according to plasma viral load or use of ART and used random-effects Poisson regression models to obtain summary transmission rates [with 95% confidence intervals, (CI)]. If there were no transmission events we estimated an upper 97.5% confidence limit. RESULTS: We identified 11 cohorts reporting on 5021 heterosexual couples and 461 HIV-transmission events. The rate of transmission overall from ART-treated patients was 0.46 (95% CI 0.19-1.09) per 100 person-years, based on five events. The transmission rate from a seropositive partner with viral load below 400 copies/ml on ART, based on two studies, was zero with an upper 97.5% confidence limit of 1.27 per 100 person-years, and 0.16 (95% CI 0.02-1.13) per 100 person-years if not on ART, based on five studies and one event. There were insufficient data to calculate rates according to the presence or absence of sexually transmitted infections, condom use, or vaginal or anal intercourse. CONCLUSION: Studies of heterosexual discordant couples observed no transmission in patients treated with ART and with viral load below 400 copies/ml, but data were compatible with one transmission per 79 person-years. Further studies are needed to better define the risk of HIV transmission from patients on ART.

Little evidence that hepatitis C virus leads to a higher risk of mortality in the absence of cirrhosis and excess alcohol intake: the Swiss Hepatitis C Cohort Study

The objective of this study was to describe the all-cause mortality of participants in the Swiss Hepatitis C Cohort compared to the Swiss general population. Patients with hepatitis C virus (HCV) infection attending secondary and tertiary care centres in Switzerland. One thousand six hundred and forty-five patients with HCV infection were followed up for a mean of over 2 years. We calculated all-cause standardized mortality ratios (SMR) and 95% confidence intervals (CI) using age, sex and calendar year-specific Swiss all-cause mortality rates. Multivariable Poisson regression was used to model the variability of SMR by cirrhotic status, HCV genotype, infection with hepatitis B virus or HIV, injection drug use and alcohol intake. Sixty-one deaths were recorded out of 1645 participants. The crude all-cause SMR was 4.5 (95% CI: 3.5-5.8). Patients co-infected with HIV had a crude SMR of 20 (95% CI: 11.1-36.1). The SMR of 1.1 (95% CI: 0.63-2.03) for patients who were not cirrhotic, not infected with HBV or HIV, did not inject drugs, were not heavy alcohol consumers (

Computer technology applications in surgical implant dentistry: a systematic review

PURPOSE: To assess the literature on accuracy and clinical performance of computer technology applications in surgical implant dentistry. MATERIALS AND METHODS: Electronic and manual literature searches were conducted to collect information about (1) the accuracy and (2) clinical performance of computer-assisted implant systems. Meta-regression analysis was performed for summarizing the accuracy studies. Failure/complication rates were analyzed using random-effects Poisson regression models to obtain summary estimates of 12-month proportions. RESULTS: Twenty-nine different image guidance systems were included. From 2,827 articles, 13 clinical and 19 accuracy studies were included in this systematic review. The meta-analysis of the accuracy (19 clinical and preclinical studies) revealed a total mean error of 0.74 mm (maximum of 4.5 mm) at the entry point in the bone and 0.85 mm at the apex (maximum of 7.1 mm). For the 5 included clinical studies (total of 506 implants) using computer-assisted implant dentistry, the mean failure rate was 3.36% (0% to 8.45%) after an observation period of at least 12 months. In 4.6% of the treated cases, intraoperative complications were reported; these included limited interocclusal distances to perform guided implant placement, limited primary implant stability, or need for additional grafting procedures. CONCLUSION: Differing levels and quantity of evidence were available for computer-assisted implant placement, revealing high implant survival rates after only 12 months of observation in different indications and a reasonable level of accuracy. However, future long-term clinical data are necessary to identify clinical indications and to justify additional radiation doses, effort, and costs associated with computer-assisted implant surgery.

Survival and failure rates of orthodontic temporary anchorage devices: a systematic review

AIM: The purpose of this study was to systematically review the literature on the survival rates of palatal implants, Onplants((R)), miniplates and mini screws. MATERIAL AND METHODS: An electronic MEDLINE search supplemented by manual searching was conducted to identify randomized clinical trials, prospective and retrospective cohort studies on palatal implants, Onplants((R)), miniplates and miniscrews with a mean follow-up time of at least 12 weeks and of at least 10 units per modality having been examined clinically at a follow-up visit. Assessment of studies and data abstraction was performed independently by two reviewers. Reported failures of used devices were analyzed using random-effects Poisson regression models to obtain summary estimates and 95% confidence intervals (CI) of failure and survival proportions. RESULTS: The search up to January 2009 provided 390 titles and 71 abstracts with full-text analysis of 34 articles, yielding 27 studies that met the inclusion criteria. In meta-analysis, the failure rate for Onplants((R)) was 17.2% (95% CI: 5.9-35.8%), 10.5% for palatal implants (95% CI: 6.1-18.1%), 16.4% for miniscrews (95% CI: 13.4-20.1%) and 7.3% for miniplates (95% CI: 5.4-9.9%). Miniplates and palatal implants, representing torque-resisting temporary anchorage devices (TADs), when grouped together, showed a 1.92-fold (95% CI: 1.06-2.78) lower clinical failure rate than miniscrews. CONCLUSION: Based on the available evidence in the literature, palatal implants and miniplates showed comparable survival rates of >or=90% over a period of at least 12 weeks, and yielded superior survival than miniscrews. Palatal implants and miniplates for temporary anchorage provide reliable absolute orthodontic anchorage. If the intended orthodontic treatment would require multiple miniscrew placement to provide adequate anchorage, the reliability of such systems is questionable. For patients who are undergoing extensive orthodontic treatment, force vectors may need to be varied or the roots of the teeth to be moved may need to slide past the anchors. In this context, palatal implants or miniplates should be the TADs of choice.

A systematic review of the performance of ceramic and metal implant abutments supporting fixed implant reconstructions

OBJECTIVES: The objective of this systematic review was to assess the 5-year survival rates and incidences of complications associated with ceramic abutments and to compare them with those of metal abutments. METHODS: An electronic Medline search complemented by manual searching was conducted to identify randomized-controlled clinical trials, and prospective and retrospective studies providing information on ceramic and metal abutments with a mean follow-up time of at least 3 years. Patients had to have been examined clinically at the follow-up visit. Assessment of the identified studies and data abstraction was performed independently by three reviewers. Failure rates were analyzed using standard and random-effects Poisson regression models to obtain summary estimates of 5-year survival proportions. RESULTS: Twenty-nine clinical and 22 laboratory studies were selected from an initial yield of 7136 titles and data were extracted. The estimated 5-year survival rate of ceramic abutments was 99.1% [95% confidence interval (CI): 93.8-99.9%] and 97.4% (95% CI: 96-98.3%) for metal abutments. The estimated cumulative incidence of technical complications after 5 years was 6.9% (95% CI: 3.5-13.4%) for ceramic abutments and 15.9% (95% CI: 11.6-21.5%) for metal abutments. Abutment screw loosening was the most frequent technical problem, occurring at an estimated cumulative incidence after 5 years of 5.1% (95% CI: 3.3-7.7%). All-ceramic crowns supported by ceramic abutments exhibited similar annual fracture rates as metal-ceramic crowns supported by metal abutments. The cumulative incidence of biological complications after 5 years was estimated at 5.2% (95% CI: 0.4-52%) for ceramic and 7.7% (95% CI: 4.7-12.5%) for metal abutments. Esthetic complications tended to be more frequent at metal abutments. A meta-analysis of the laboratory data was impossible due to the non-standardized test methods of the studies included. CONCLUSION: The 5-year survival rates estimated from annual failure rates appeared to be similar for ceramic and metal abutments. The information included in this review did not provide evidence for differences of the technical and biological outcomes of ceramic and metal abutments. However, the information for ceramic abutments was limited in the number of studies and abutments analyzed as well as the accrued follow-up time. Standardized methods for the analysis of abutment strength are needed.

A systematic review of the survival and complication rates of implant supported fixed dental prostheses with cantilever extensions after an observation period of at least 5 years

OBJECTIVE: The aim of this systematic review was to assess the survival rates of short-span implant-supported cantilever fixed dental prostheses (ICFDPs) and the incidence of technical and biological complications after an observation period of at least 5 years. MATERIAL AND METHODS: An electronic MEDLINE search supplemented by manual searching was conducted to identify prospective or retrospective cohort studies reporting data of at least 5 years on ICFDPs. Five- and 10-year estimates for failure and complication rates were calculated using standard or random-effect Poisson regression analysis. RESULTS: The five studies eligible for the meta-analysis yielded an estimated 5- and 10-year ICFDP cumulative survival rate of 94.3% [95 percent confidence interval (95% CI): 84.1-98%] and 88.9% (95% CI: 70.8-96.1%), respectively. Five-year estimates for peri-implantitis were 5.4% (95% CI: 2-14.2%) and 9.4% (95% CI: 3.3-25.4%) at implant and prosthesis levels, respectively. Veneer fracture (5-year estimate: 10.3%; 95% CI: 3.9-26.6%) and screw loosening (5-year estimate: 8.2%; 95% CI: 3.9-17%) represented the most common complications, followed by loss of retention (5-year estimate: 5.7%; 95% CI: 1.9-16.5%) and abutment/screw fracture (5-year estimate: 2.1%; 95% CI: 0.9-5.1%). Implant fracture was rare (5-year estimate: 1.3%; 95% CI: 0.2-8.3%); no framework fracture was reported. Radiographic bone level changes did not yield statistically significant differences either at the prosthesis or at the implant levels when comparing ICFDPs with short-span implant-supported end-abutment fixed dental prostheses. CONCLUSIONS: ICFDPs represent a valid treatment modality; no detrimental effects can be expected on bone levels due to the presence of a cantilever extension per se.

A systematic review of the clinical performance of CAD/CAM single-tooth restorations

PURPOSE: This systematic review sought to determine the long-term clinical survival rates of single-tooth restorations fabricated with computer-aided design/computer-assisted manufacture (CAD/CAM) technology, as well as the frequency of failures depending on the CAD/CAM system, the type of restoration, the selected material, and the luting agent. MATERIALS AND METHODS: An electronic search from 1985 to 2007 was performed using two databases: Medline/PubMed and Embase. Selected keywords and well-defined inclusion and exclusion criteria guided the search. All articles were first reviewed by title, then by abstract, and subsequently by a full text reading. Data were assessed and extracted by two independent examiners. The pooled results were statistically analyzed and the overall failure rate was calculated by assuming a Poisson-distributed number of events. In addition, reported failures were analyzed by CAD/CAM system, type of restoration, restorative material, and luting agent. RESULTS: From a total of 1,957 single-tooth restorations with a mean exposure time of 7.9 years and 170 failures, the failure rate was 1.75% per year, estimated per 100 restoration years (95% CI: 1.22% to 2.52%). The estimated total survival rate after 5 years of 91.6% (95% CI: 88.2% to 94.1%) was based on random-effects Poisson regression analysis. CONCLUSIONS: Long-term survival rates for CAD/CAM single-tooth Cerec 1, Cerec 2, and Celay restorations appear to be similar to conventional ones. No clinical studies or randomized clinical trials reporting on other CAD/CAM systems currently used in clinical practice and with follow-up reports of 3 or more years were found at the time of the search.

H-ficolin serum concentration and susceptibility to fever and neutropenia in paediatric cancer patients

H-ficolin (Hakata antigen, ficolin-3) activates the lectin pathway of complement similar to mannose-binding lectin. However, its impact on susceptibility to infection is currently unknown. This study investigated whether the serum concentration of H-ficolin at diagnosis is associated with fever and neutropenia (FN) in paediatric cancer patients. H-ficolin was measured by time-resolved immunofluorometric assay in serum taken at cancer diagnosis from 94 children treated with chemotherapy. The association of FN episodes with H-ficolin serum concentration was analysed by multivariate Poisson regression. Median concentration of H-ficolin in serum was 26 mg/l (range 6-83). Seven (7%) children had low H-ficolin (< 14 mg/l). During a cumulative chemotherapy exposure time of 82 years, 177 FN episodes were recorded, 35 (20%) of them with bacteraemia. Children with low H-ficolin had a significantly increased risk to develop FN [relative risk (RR) 2.24; 95% confidence interval (CI) 1.38-3.65; P = 0.004], resulting in prolonged duration of hospitalization and of intravenous anti-microbial therapy. Bacteraemia occurred more frequently in children with low H-ficolin (RR 2.82; CI 1.02-7.76; P = 0.045). In conclusion, low concentration of H-ficolin was associated with an increased risk of FN, particularly FN with bacteraemia, in children treated with chemotherapy for cancer. Low H-ficolin thus represents a novel risk factor for chemotherapy-related infections.

Effect of initial treatment strategy on survival of patients with advanced-stage Hodgkin's lymphoma: a systematic review and network meta-analysis

BACKGROUND Several treatment strategies are available for adults with advanced-stage Hodgkin's lymphoma, but studies assessing two alternative standards of care-increased dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPescalated), and doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD)-were not powered to test differences in overall survival. To guide treatment decisions in this population of patients, we did a systematic review and network meta-analysis to identify the best initial treatment strategy. METHODS We searched the Cochrane Library, Medline, and conference proceedings for randomised controlled trials published between January, 1980, and June, 2013, that assessed overall survival in patients with advanced-stage Hodgkin's lymphoma given BEACOPPbaseline, BEACOPPescalated, BEACOPP variants, ABVD, cyclophosphamide (mechlorethamine), vincristine, procarbazine, and prednisone (C[M]OPP), hybrid or alternating chemotherapy regimens with ABVD as the backbone (eg, COPP/ABVD, MOPP/ABVD), or doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone combined with radiation therapy (the Stanford V regimen). We assessed studies for eligibility, extracted data, and assessed their quality. We then pooled the data and used a Bayesian random-effects model to combine direct comparisons with indirect evidence. We also reconstructed individual patient survival data from published Kaplan-Meier curves and did standard random-effects Poisson regression. Results are reported relative to ABVD. The primary outcome was overall survival. FINDINGS We screened 2055 records and identified 75 papers covering 14 eligible trials that assessed 11 different regimens in 9993 patients, providing 59 651 patient-years of follow-up. 1189 patients died, and the median follow-up was 5·9 years (IQR 4·9-6·7). Included studies were of high methodological quality, and between-trial heterogeneity was negligible (τ(2)=0·01). Overall survival was highest in patients who received six cycles of BEACOPPescalated (HR 0·38, 95% credibility interval [CrI] 0·20-0·75). Compared with a 5 year survival of 88% for ABVD, the survival benefit for six cycles of BEACOPPescalated is 7% (95% CrI 3-10)-ie, a 5 year survival of 95%. Reconstructed individual survival data showed that, at 5 years, BEACOPPescalated has a 10% (95% CI 3-15) advantage over ABVD in overall survival. INTERPRETATION Six cycles of BEACOPPescalated significantly improves overall survival compared with ABVD and other regimens, and thus we recommend this treatment strategy as standard of care for patients with access to the appropriate supportive care.

Impact of unlinked deaths and coding changes on mortality trends in the Swiss National Cohort

BACKGROUND Results of epidemiological studies linking census with mortality records may be affected by unlinked deaths and changes in cause of death classification. We examined these issues in the Swiss National Cohort (SNC). METHODS The SNC is a longitudinal study of the entire Swiss population, based on the 1990 (6.8 million persons) and 2000 (7.3 million persons) censuses. Among 1,053,393 deaths recorded 1991-2007 5.4% could not be linked using stringent probabilistic linkage. We included the unlinked deaths using pragmatic linkages and compared mortality rates for selected causes with official mortality rates. We also examined the impact of the 1995 change in cause of death coding from version 8 (with some additional rules) to version 10 of the International Classification of Diseases (ICD), using Poisson regression models with restricted cubic splines. Finally, we compared results from Cox models including and excluding unlinked deaths of the association of education, marital status, and nationality with selected causes of death. RESULTS SNC mortality rates underestimated all cause mortality by 9.6% (range 2.4%-17.9%) in the 85+ population. Underestimation was less pronounced in years nearer the censuses and in the 75-84 age group. After including 99.7% of unlinked deaths, annual all cause SNC mortality rates were reflecting official rates (relative difference between -1.4% and +1.8%). In the 85+ population the rates for prostate and breast cancer dropped, by 16% and 21% respectively, between 1994 and 1995 coincident with the change in cause of death coding policy. For suicide in males almost no change was observed. Hazard ratios were only negligibly affected by including the unlinked deaths. A sudden decrease in breast (21% less, 95% confidence interval: 12%-28%) and prostate (16% less, 95% confidence interval: 7%-23%) cancer mortality rates in the 85+ population coincided with the 1995 change in cause of death coding policy. CONCLUSIONS Unlinked deaths bias analyses of absolute mortality rates downwards but have little effect on relative mortality. To describe time trends of cause-specific mortality in the SNC, accounting for the unlinked deaths and for the possible effect of change in death certificate coding was necessary.

Short- and long-term mortality and causes of death in HIV/tuberculosis patients in Europe

Mortality of HIV/tuberculosis (TB) patients in Eastern Europe is high. Little is known about their causes of death. This study aimed to assess and compare mortality rates and cause of death in HIV/TB patients across Eastern Europe and Western Europe and Argentina (WEA) in an international cohort study. Mortality rates and causes of death were analysed by time from TB diagnosis (<3 months, 3-12 months or >12 months) in 1078 consecutive HIV/TB patients. Factors associated with TB-related death were examined in multivariate Poisson regression analysis. 347 patients died during 2625 person-years of follow-up. Mortality in Eastern Europe was three- to ninefold higher than in WEA. TB was the main cause of death in Eastern Europe in 80%, 66% and 61% of patients who died <3 months, 3-12 months or >12 months after TB diagnosis, compared to 50%, 0% and 15% in the same time periods in WEA (p<0.0001). In multivariate analysis, follow-up in WEA (incidence rate ratio (IRR) 0.12, 95% CI 0.04-0.35), standard TB-treatment (IRR 0.45, 95% CI 0.20-0.99) and antiretroviral therapy (IRR 0.32, 95% CI 0.14-0.77) were associated with reduced risk of TB-related death. Persistently higher mortality rates were observed in HIV/TB patients in Eastern Europe, and TB was the dominant cause of death at any time during follow-up. This has important implications for HIV/TB programmes aiming to optimise the management of HIV/TB patients and limit TB-associated mortality in this region.

Risk Factors and Outcomes for Late Presentation for HIV-Positive Persons in Europe: Results from the Collaboration of Observational HIV Epidemiological Research Europe Study (COHERE)

Background Few studies have monitored late presentation (LP) of HIV infection over the European continent, including Eastern Europe. Study objectives were to explore the impact of LP on AIDS and mortality. Methods and Findings LP was defined in Collaboration of Observational HIV Epidemiological Research Europe (COHERE) as HIV diagnosis with a CD4 count <350/mm3 or an AIDS diagnosis within 6 months of HIV diagnosis among persons presenting for care between 1 January 2000 and 30 June 2011. Logistic regression was used to identify factors associated with LP and Poisson regression to explore the impact on AIDS/death. 84,524 individuals from 23 cohorts in 35 countries contributed data; 45,488 were LP (53.8%). LP was highest in heterosexual males (66.1%), Southern European countries (57.0%), and persons originating from Africa (65.1%). LP decreased from 57.3% in 2000 to 51.7% in 2010/2011 (adjusted odds ratio [aOR] 0.96; 95% CI 0.95–0.97). LP decreased over time in both Central and Northern Europe among homosexual men, and male and female heterosexuals, but increased over time for female heterosexuals and male intravenous drug users (IDUs) from Southern Europe and in male and female IDUs from Eastern Europe. 8,187 AIDS/deaths occurred during 327,003 person-years of follow-up. In the first year after HIV diagnosis, LP was associated with over a 13-fold increased incidence of AIDS/death in Southern Europe (adjusted incidence rate ratio [aIRR] 13.02; 95% CI 8.19–20.70) and over a 6-fold increased rate in Eastern Europe (aIRR 6.64; 95% CI 3.55–12.43). Conclusions LP has decreased over time across Europe, but remains a significant issue in the region in all HIV exposure groups. LP increased in male IDUs and female heterosexuals from Southern Europe and IDUs in Eastern Europe. LP was associated with an increased rate of AIDS/deaths, particularly in the first year after HIV diagnosis, with significant variation across Europe. Earlier and more widespread testing, timely referrals after testing positive, and improved retention in care strategies are required to further reduce the incidence of LP.

The Incidence of AIDS-Defining Illnesses at a Current CD4 Count >=200 Cells/ L in the Post-Combination Antiretroviral Therapy Era

Background. Few studies consider the incidence of individual AIDS-defining illnesses (ADIs) at higher CD4 counts, relevant on a population level for monitoring and resource allocation. Methods. Individuals from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) aged ≥14 years with ≥1 CD4 count of ≥200 µL between 1998 and 2010 were included. Incidence rates (per 1000 person-years of follow-up [PYFU]) were calculated for each ADI within different CD4 strata; Poisson regression, using generalized estimating equations and robust standard errors, was used to model rates of ADIs with current CD4 ≥500/µL. Results. A total of 12 135 ADIs occurred at a CD4 count of ≥200 cells/µL among 207 539 persons with 1 154 803 PYFU. Incidence rates declined from 20.5 per 1000 PYFU (95% confidence interval [CI], 20.0–21.1 per 1000 PYFU) with current CD4 200–349 cells/µL to 4.1 per 1000 PYFU (95% CI, 3.6–4.6 per 1000 PYFU) with current CD4 ≥ 1000 cells/µL. Persons with a current CD4 of 500–749 cells/µL had a significantly higher rate of ADIs (adjusted incidence rate ratio [aIRR], 1.20; 95% CI, 1.10–1.32), whereas those with a current CD4 of ≥1000 cells/µL had a similar rate (aIRR, 0.92; 95% CI, .79–1.07), compared to a current CD4 of 750–999 cells/µL. Results were consistent in persons with high or low viral load. Findings were stronger for malignant ADIs (aIRR, 1.52; 95% CI, 1.25–1.86) than for nonmalignant ADIs (aIRR, 1.12; 95% CI, 1.01–1.25), comparing persons with a current CD4 of 500–749 cells/µL to 750–999 cells/µL. Discussion. The incidence of ADIs was higher in individuals with a current CD4 count of 500–749 cells/µL compared to those with a CD4 count of 750–999 cells/µL, but did not decrease further at higher CD4 counts. Results were similar in patients virologically suppressed on combination antiretroviral therapy, suggesting that immune reconstitution is not complete until the CD4 increases to >750 cells/µL.